Two-step chlorination of heterocyclic tertiary amines to produce compounds having an-n=cci-radical



United States Patent Ofice Patented June 13, 1068 TWO-STEP CHLGRINATION F HETERQCYCLIC TERTIARY AMINES TO PRKJDUQE C(DMPUUNDS HAVENG AN -N=CCi-RADHCAIL Hans I-loitschmidt and Wilfried Zecher, Cologne-Staminheim, Germany, assignors to Farhentabriken Bayer Alctiengesellschaft, Leverkusen, Germany, a corporation of Germany No Drawing. Original application Aug. 28, 1962, Ser. No. 220,070, new Patent No. 3,251,760, dated h iay 17, 1966. Divided and this application Apr. 7, 1965, Ser. No. 446,402

Claims. (Cl. 204-158) in which R and R separately stand for an alkyl or aryl group which may be substituted by halogen, cyano, aryl, alkyl, amino or imino groups, and in which R and R together with =N- jointly stand for an isocyclic or heterocyclic ring, and in which X stands for an acyl group, with chlorine at temperatures below 140 C. to the extent that all replaceable hydrogen atoms are replaced by chlorine atoms,

and then (2) treating the chlorination product thus obtained with chlorine at temperatures between 140 and 300 C., whereby an acyl chloride is spit off.

Ithas been found that organic nitrogen compounds which contain the --N=CCl-radical can be obtained by (1) reacting an amine having the formula:

\N-R3 112 in which R and R separately stand for an alkyl or aryl group which may be substituted by halogen, cyano, aryl, alkyl, amino or imino groups, and in which R and R together with =N- jointly stand for an isocyclic or heterocyclic ring and in which R stands for a methyl or an aryl group which can be further substituted, with chlorine at temperatures below 140 C. to the extent that all replaceable hydrogen atoms are replaced by chlorine atoms,

and then (2) treating the chlorination product thus, obtained with chlorine at temperatures between 140 and 300 C., whereby an alkyl chloride is split olf.

It is important to conduct the reaction with the temperature so controlled that the amino compounds are so completely saturated with chlorine at temperatures below 140 C. that in the subsequent chlorinating dissociation, which takes place between 140 and 300 C., condensation and polymerization reactions are prevented. Furthermore, when chlorine is introduced at lower temperatures carbon atoms which are in the alpha position with reference to nitrogen acquire a positive charge which favors subsequent dissociation rather than any side reaction.

The amines mentioned are, in general, such strong bases that their hydrochlorides precipitate at the beginning of chlorination. Therefore, hydrochlorides or alkylation products (with alkyl halogenide) of these amines may be introduced from the very beginning. As chlorination proceeds the basicity of the amines is lowered to such a degree that the ammonium compound becomes unstable and hydrogen chloride or the chlorinated alkyl group is split olf again. If the reaction is interrupted at this stage the chlorinated amines may be distilled off and thus separated. With aryl substituted amines it is possible to effect the nuclear chlorination by quaternization.

Examples of starting materials fulfilling the foregoing requirements are:

N ,N-dimethylaminoacetonitrile N ,N-dimethylsminopropionitrile CHa In addition to a substantial chlorination of the whole molecule there may be consequential reactions with which this invention is also concerned. Ring structures, for example, N,N'-dimethylpiperazine are stabilized by a transformation to the aromatic state. Urotropin (hexamethylenetetramine) is split during chlorination in such a manner that cyanuric chloride is obtained as a reaction product. In the case of dimethylaminoacetonitrile the cyano radical is split oit and the molecude becomes dimeric Chlorination can also be carried out in a solvent, especially if ammonium salts with high melting points are used as starting materials. Suitable solvents are, for example, 1,2,4-trichlorobenzene, chloroform, tetrachloroethane and phthayl chloride.

The invention is the more surprising in that direct chlorination of aliphatic or aliphatic-aromatic amines or of their salts have hitherto been described in few cases. It is, for example, known that the addition product of chlorine and trimethtylamine sometimes dissociates explosively at 35 C. (see Houben-Weyl, Methoden der organischen Chemie, vol. V/3, page 642).

Some of the products obtainable according to the process of the present invention are known. The known compounds are, however, only obtainable with difficulty, by other methods. They are valuable products for the preparation of pest control agents, herbicides, dyestuffs and plastics. Further, they can as such be used as insecticides and nematocides, because of their high activity against spiders, mites flies and fungi. a

As a typical example of the high nematocidal activity of the products of the present invention the treatment of chloride is shown below.

Soil is heavily infested with the root cyst nematode Meloidogyrr incognita. 25, 50, 100 and 200 p.p.m. of 2,4, 6-trichlorophenylimidocarbonyl chloride are added to one liter of infested soil. The active agent is applied in admixture with talcum, this mixture containing 1% of active ingredient.

One week after the preparation, seed of soft lettuce was so put into the soil. After a 4 weeks period the plants were checked for cyst formation. The following table shows the effectiveness of the compound in preventing cyst formation.

P.p.m.: Percent 25 50 100 100 200 100 The following examples are given for the purpose of illustrating the present invention:

EXAMPLE 1 116 parts by weight of 1,2-bis(dimethylamino ethane are dissolved in 1000 parts by volume of 1,2,4-trichlorobenzene. A weak current of chlorine is then introduced and the strongly exothermic reaction is restrained by cooling so that the temperature remains between 7080 C. When the exothermic reaction has subsided, chlorination is continued while the mixture is irradiated with ultraviolet light, and the temperature rise is controlled in such a way that within one hour a rise of 10-15 C. takes place. Subsequently chlorination is continued for a further 3 hours at ZOO-230 C., then nitrogen is blown through and the solution left to cool. On cooling, most of the ethylene- 1,2-bis(imidocarbonyl chloride) precipitates as crystals, the remainder being obtained by further evaporating the solution.

Melting point (toluene), 166 C. (white flakes).

Analysis (C Cl N Found: C, 13.56%; N, 7.90%; Cl, 79.05%. Calculated: C, 13.3%; N, 7.8%; Cl, 79.0%.

Determination of molecular weight (after period in hexachlorobenzene): Found 365. Calculated: 360.

The same compound can be obtained by chlorinating dimethylaminoacetonitrile with dissociation of cyanogen chloride by chlorinating under the same conditions as described hereinbefore in this example.

EXAMPLE 2 140 parts by weight of hexamethylenetetramine are suspended in 600 cc. of tetrachloroethane and a gentle stream of chlorine is passed therethrough at room temperature, whereby the temperature quickly rises to 8090 C. and the suspension changes to a thick paste. Subsequently the temperature is slowly raised to 140 C. (10 degrees per hour). Chlorination is continued while the mixture is irradiated with the ultraviolet light until most of the substance has dissolved and there is only a small residue left. After filtering off the residue the tetrachloroethane is distilled off and the remaining yellow oil is further chlorinated at ZOO-240 C. During chlorination large quantities of a white substance of boiling point 190 C. and melting point 146 C. sublime in the condenser. The same substance is obtained by the subsequent distillation of the chlorination product. The substance was identified by analysis, mixed melting point and spectrum as cyanuric chloride.

EXAMPLE 3 355 parts by weight (6 mols.) of trimethylamine are dissolved in 1000 parts by volume of 1,2,4-trichlorobenzene while the solution is cooled with ice. Under continued cooling hydrogen chloride is introduced to saturation point. A pasty suspension of the hydrochloride in trichlorobenzene is obtained, into which chlorine is introduced at C. for 20 hours while stirring and irradiating the mixture with ultraviolet light.

The reaction product, a clear dark brown solution, is fractionated in vacuum through a silvered column. The solvent, boiling point 90-95 C. at 16 mm. Hg is separated from the other fractions, boiling point 60-90 C. at 16 mm. Hg and 95-210 C., and a mixture of chlorinated amines is thus obtained which is chlorinated for 4 hours at C. and for 11 hours at 200 C., while the mixture is irradiated with ultra violet light. The product is again fractionated in vacuum through a silvered column. The trichloromethylimidocarbonyl chloride distils over at boiling point 65-67" C. at 17 mm. Hg 11 1.5540.

is? Analysis (C Cl N): Molecular weight: 215.3. Calculated: C=11.16%; Cl=82.35%; N=6.51%. Found: C=l1.58%, 11.65%; Cl=82.1%; N=6.4%, 6.7%.

EXAMPLE 4 Chlorine is passed in to a suspension of 576 grams (4 mols) of finely ground 1-dimethylamino-2-chloroethane hydrochloride in 700 cc. of 1,2,4-trichlorobenzene While stirring and irradiating the mixture with ultraviolet light. After about 40 hours at 130-140 C. the salt has dissolved with liberation of hydrogen chloride. The brown reaction liquid is further chlorinated for 3 hours at 160 C. and for 16 hours at 210 C. The chloroform liberated during the reaction may be separated with a conventional water trap. After removing hydrogen chloride and excess chlorine by means of nitrogen the reaction mixture is fractionated in vacuum over a silvered column. At boiling point 120-121 C. and 13 mm. Hg pentachloroethylimidocarbonyl chlOride distils over as a colorless liquid. 11 1.5530.

Analysis (C CI N): Molecular weight: 298.24. Calculated: C, 12.09%; Cl, 83.25%; N, 4.70%. Found: C, 12.61%;Cl, 82.55%;N. 5.05%.

EXAMPLE 5 Trichlorophenylimidocarbonyl chloride 400 grams (2.33 mols) of N-phenyl-N,N,N-trimethylammonium chloride are suspended in 700 cc. of 1,2,4-trichlorobenzene. The mixture is then chlorinated for 13 hours at 100 C. While stirring and irradiating it with an ultraviolet lamp. The ammonium salt dissolves and, with liberation of hydrogen chloride, a yellow and a dark brown liquid are obtained which remain separated in two phases. While continuing the introduction of chlorine the temperature is raised by 20 C. every two hours until 200 C. has been reached, when chlorination is continued for a further 7 hours at this temperature. The reaction mixture is fractionated in vacuum, the solvent is separated and the residue chlorinated again at 240 C. for 18 hours. The reaction product is then fractionated through a silvered column. The trichlorophenylimidocarbonyl chloride distils over as a faintly yellow liquid with a boiling point of l48l53 C. at 15 mm. Hg. 11 1.5950.

Analysis (C H Cl N) Molecular weight: 277.4. Calculated: C, 30.32%; H, 0.73%; N, 5.05%; Cl 63.91%. Found: C, 30.04%, 30.36%; H, 0.76%, 0.89%; N, 5.23%, 5.25%; CI, 64.4%, 64.5%.

EXAMPLE 6 2,3,5,6-tetrachloropyrazine from 1,4-dimethylpiperazine A solution of 80 grams (0.7 mol) of 1,4-dimethylpiperazine in 150 cc.. of chloroform is chlorinated, while cooled with ice, for 8 hours at 30 C. After the reaction, strongly exothermic at the beginning, has subsided, 200 cc. of 1,2,6-trichlorobenzene are added, the chloroform is distilled oh? and the suspension further chlorinated at higher temperatures finally at 200 C. While it is irradiated with ultraviolet light. Distillation under vacuum yields at boiling point 100-145 C. and 15 mm. Hg a fraction from which 2,3,5,6-tetrachloropyrazine precipitates, on cooling, as colorless crystals. After recrystallization from methanol colorless flakes of melting point 9799 C. are obtained.

Analysis CQCIQNZ: Molecular weight: 217.9. Calculated: C, 22.05%; Cl 65.09%. Found: C, 22.41%, 22.34%; CI, 64.7%, 65.0%.

EXAMPLE 7 2,3,5,6-tetrachloropyrazine from 1,4-bis(2-hydroxyethyl) piperazine 6 250 cc. of 1,2,4-trichlorobcnzene are added to 87 grams (0.5 mil) of N,N-bisethanolpiperazine while cooled with ice and the mixture is chlorinated for 6 hours at 25 C. under irradiation with ultraviolet light. It is then heated and chlorination continued while the temperature is slowly raised to 200 C. Subsequently the reaction mixture is fractionated in vacuum. At boiling point -l40 C. 14 mm. Hg a fraction is obtained from which tetrachlorpyrazine crystallizes on cooling. Recrystallization from acetonit-rile or methanol yields colorless flakes of melting point 9699 C.

Analysis (C Cl N Molecular weight: 217.9. Calcuglated: C, 22.05%; N, 12.86%. Found: C, 22.40%, 22.42%; N, 12.65%, 12.66%.

EXAMPLE s Tetracl'iloropyridines and pentachloropyridine from N- methylpiperidine Chlorine is passed at 10 C. into a solution of 198 grams (2 mols) of N-methylpiperidine in 200 cc. of chloroform while cooling with ice. A pasty suspension is obtained which is then chlorinated at 20 C., while the mixture is stirred and irradiated with ultraviolet light, until the solution becomes clear. The temperature is then slowly raised, the chloroform distilled off at 60 C., and while chlorine is passed under further irradiation with ultraviolet light the mixture is maintained for several hours each at C., C., C., C. and finally at 200 C. Subsequently nitrogen is blown through the mixture and it is fractionated in vacuum. At boiling point l09-125 C. at a pressure of 12 mm. Hg, 234 grams tetrachloropyridine distils over. A fraction of boiling point 125-140 C. at a pressure of 12 mm. Hg, yields when cooled a solid precipitate of 31 grams (=6.2% of the theoretical) of pentachloropyridine (from ethanol, colorless polyhedrons having a melting point of 125-127 C.) and a mother liquor containing 22 grams of tetrachloropyridine. The total yield of isomeric tetrachloropyridines amounts to 256 grams (59% of the theoretical).

Analysis (C Cl N): Molecular weight: 251.4. Calculated: C, 23.89%; Cl, 70.52%; N,5.57%. Found: C, 24.04%, 24.20%; Cl, 70.45%, 70.65%; N, 5.71%, 5.76%.

Analysis (C HCl N): Molecular weight: 216.9. Calculated: C, 27.69%; H, 0.47%; N, 6.46%. Found: C, 27.20%, 27.46%; H, 0.5%, 0.5%; N, 6.41%, 6.41%.

EXAMPLE 9 366 parts by weight of dimethylaniline are chlorinated, first without irradiation, at a temperature between 20- 60 C. until the reaction stops being exothermic (chlorination of the nucleus). From a temperature of 60 C. onwards, the chlorination is then continued under ultraviolet irradiation. The temperature is raised in such a Way that a temperature rise of about 10 C. per hour takes place. When the temperature has reached -220 C., chlorination is continued for a further 3 hours at this temperature. Nitrogen is then passed through in order to remove any dissolved chlorine.

During the subsequent vacuum-distillation trichlorphenylimidocarbonyl chloride distils over at a pressure of 0.3 mm. Hg at S891 C. Yield: 648 parts by Weight, n =1.5970.

Analysis (C7H2NCl5): Calculated: C, 30.15%; H, 0.72%;N, 5.06%; Cl, 64.2%. Found: C, 30.17%; H 0.78%; N, 5.65%; C1, 64.4%.

EXAMPLE 10 816 parts by weight of Z-dimethylamino-4,6-dichlorotriazine are melted at 125 C. and chlorine is introduced into the melt at a temperature of 130-150 C. After about 4 hours when the exothermic reaction has subsided, the chlorination is continued under ultraviolet irradiation and the temperature raised by 10 C. per hour until it reaches 220 C. At this temperature chlorine is introduced, while the mixture is irradiated for about 8 hours. The product is then fractionated under a water-jet vacuum. After first runnings consisting of trichloromethylimidocarbonyl chloride and cyanuric chloride the compound of the formula distils over at a boiling point of 126-128 C./l2 mm. Hg. Yield: 672 parts by weight, 1.5751.

Analysis (C N Cl Calculated: C, 19.5%; N, 22.8%; CI, 57.6%. Found: C, 19.62%; N, 22.87%; Cl, 56.97.

The product is identical with the so-called tetrameric cyanogen chloride which is formed in small quantities in the trimerization of cyanogen chloride into cyanuric chloride.

EXAMPLE 11 110 parts by weight of 2,4-bis(dimethylamino)-6- chlorotriazine-l,3,5 are chlorinated as described in Example 10. Upon fractionating, there are obtained, after first runnings of cyanuric chloride and trichlorornethylimidocarbonyl chloride 59 parts by weight of the compound.

Cl Cl A mixture of 385 parts by weight of N,N-dimethylpentachloraniline and 250 parts by volume of chloroform is chlorinated at 40-55 C. while irradiating it with ultraviolet light, the mixture being cooled with ice-water because of the strongly exothermic reaction. The temperature of the reaction mixture is then slowly raised, as described in Example 9 and during which period the chloroform distils 01f, finally the mixture is kept for 8 hours at ZOO-230 C. Excess chlorine is then removed by blowing through nitrogen and pentachlorophenylimidocarbonyl chloride having the foregoing formula is distilled off under high vacuum. It boils at a pressure of 0.1 mm. Hg at 134138 C. and has a refractive index 11 =1.6258.

Analysis (C Cl N): Calculated: C, 24.3%; N, 4.05%; Cl, 70.6%. Found: C, 24.4%; N, 4.5%; Cl, 71.5%.

EXAMPLE 13 8 that was obtained by condensation of trichlorophenylimidocarbonyl chloride (Example 5) and dimethylamine [B.P. 128-131 C./0.09 mm. Hg] are chlorinated as described in Example 12. Excess chlorine is then removed by blowing through nitrogen and the reaction product distilled 01f under a high vacuum. Boiling point l38-142 C. at 0.1 mm. Hg; n =1.6080.

Analysis (C H CI N Calculated: C, 28.3%; H, 0.59%; N, 8.25%; Cl, 63.0%. Found: C, 28.47%; H, 0.65%; N, 8.22%; Cl, 63.55%.

EXAMPLE 14 A mixture of 366 parts by weight of 2-N,N-dimethy.laminotoluene and 300 parts by volume of chloroform is chlorinated as described in Example 12 and Worked up. The reaction product boils at a pressure of 0.05 mm. Hg at l30-136 C.; n =1.6lO7.

Analysis (C HgCl N): Calculated: C, 29.4%; H, 0.92%; N, 4.3%; Cl, 65.4%. Found: C, 28.96%; H, 0.91%; N, 4.28%; CI, 65.45%.

EXAMPLE 15 N- i Cl (ll-( ll 240 parts by weight of 2,5-dimethylamino-3,6-dichloro-p-benzoquinone and 1500 parts by volume of trichlorobenzene are chlorinated at room temperature under ultraviolet irradiation. Without external supply of heat the temperature of the mixture rises to C. After the exothermic reaction has subsided the mixture is further chlorinated as described in Example 9. The solvent is finally distilled off and a product having the foregoing formula is obtained in the form of pale yellow crystals having a melting point of 264-266 C. (after recrystallization from xylene), besides a red oil of unknown constitution.

Analysis (C Cl N O Calculated: C, 32.2%; N, 9.4%; Cl, 47.6%; 0, 10.7%. Found: C, 32.7%; N, 9.3%; Cl, 46.7%; 0, 11.5%.

Hydrolyzable chlorine calculated 23.8%; found 23.5%.

EXAMPLE 16 K i C=NC Cl2-C Cl2-C Clz-O-Cl To 397 parts by weight of N-methylpy-rrolidone are added 500 parts by Weight of 1,24-trichlorobenzene; the mixture is chlorinated at C. while the mixture is stirred and irradiated with ultraviolet light. After 16 hours the temperature is raised by 20 C. every 3 hours while chlorine is continually introduced and then the mixture kept at 220-230" C. for 20 hours. Hydrogen chloride and excess chlorine are then driven out with nitrogen and the reaction mixture is subjected to fractional distillation in a silver-lined column. 3 chloroformylhexachloropropylimidoearbonyl chloride distils over at a pressure of 15 mm. Hg at 188-189 C. and forms a crystalline solid in the receiver. By recrystallization from acetonitrile the product is obtained in the form of colorless polyhedrons having a melting point of 98-101 C.

Analysis.-Molecular weight 409.2. Calculated for C C1 NO: C, 14.68%; Cl, 77.99%; N,3.42%; O, 3.91%. Found: C, 14.84%; Cl, 77.75%; N, 3.63%; O, 4.11%; C, 14.86%; Cl, 77.90%; N, 3.63%; O, 4.31%.

We claim:

1. A process for the production of an organic com- 9 pound containing chlorine and nitrogen combined in the -N=CCl-radical which comprises (A) reacting an amino compound selected from the group consisting of (i) amines of the formula wherein R and R taken together with the nitrogen to which each is attached stand for a heterocyclic radical of the group consisting of five and six membered heterocyclic radicals containing from 1 to 2 nitrogen atoms wherein nitrogen is the only heterocyclic atom,

R stands for a radical selected from the group consisting of lower alkyl, chloro-substituted lower alkyl, cyano-substituted lower alkyl, phenyl-substituted lower alkyl, phenyl, chlorophenyl, cyanophenyl, nitrophenyl, naphthyl,

benzoquinonyl, chloro-substituted triazinyl chloroand amino-substituted triazinyl,

R N:(l]

wherein R is a member selected from the group consisting of chlorophenyl, lower chloro alkyl and phenyl, and R stands for a member selected from the group consisting of chloro and amino, and

wherein R is lower alkyl, and R and R are separately lower alkyl and when taken together with the nitrogen to which they are attached a 5 to 6 membered heterocyclic group containing nitrogen as the only heterocylic atom (ii) salts of said amines with hydrogen halides, and

(iii) quaternary salts of said amines with alkyl halides, with chlorine while it is irradiated with ultraviolet light at a temperature below 140 C. for such a period that replaceable hydrogen atoms of the amino compound are replaced by chlorine atoms, (B) further treating the reaction mixture containing the chlorine-containing compound with additional chlorine at a higher temperature between 140 C. and 300 C. while it is irradiated with ultraviolet light, and (C) recovering the resulting organic compound containing nitrogen and chlorine combined in an N=CC1-radical. 2. A process for the production of an organic nitrogen compound containing chlorine and nitrogen combined in the --N=CCl-radical which comprises t0 (A) reacting a compound selected from the group consisting of (i) amines of the formula in which R and R together with =N- jointly stand for ring selected from the group consisting of five and six membered heterocyclic rings containing from 1 to 2 nitrogen atoms wherein nitrogen is the only heteroatom, and in which R stands for a member selected from the group consisting of alkyl and aryl radicals and their halogen, cyano, aryl, alkyl, amino and imino derivatives, (ii) salts of said amines with hydrogen halides, and

(iii) quaternary salts of said amines with hydrogen halides, with chlorine at temperatures below C. until all replaceable hydrogen atoms are replaced by chloroatoms, (B) treating the chlorination product thus obtained with chlorine at temperatures between 140 and 300 (3., whereby alkyl chloride is split 0E, and

(C) recovering the organic nitrogen compound from the reaction mixture.

3. A process for the production of 2,3,5,6-tetrachloropyrazine which comprises reacting a solution of 1,4-dimethylpiperazine in chloroform with chlorine at a temperature of approximately 30 C., while it is irradiated with ultraviolet light, separating the resulting product from the chloroform and suspending the product in 1,2,4- trichlorobenzene, reacting the suspension of the product in 1,2,4-trichlorobenzene with chlorine at increasing temperatures up to 200 C. while it is irradiated with ultraviolet light, and subsequently separating the 2,3,5,6-tetrachloropyrazine thus produced.

4. A process for the production of 2,3,5,6-tetrachloropyrazine which comprises reacting a suspension of 1,4- bis(2-hydroxyethyl)piperazine with chlorine at a temperature of approximately 25 C. while it is irradiated with ultraviolet light, continuing the reaction with chlorine at a temperature gradually increasing to 200 C., and subsequently recovering the 2,3,5,6-tetrachloropyrazine thus produced.

5. A process for the production of tetrachloropyridine and pentachloropyridine which comprises reacting a solution of l-methylpiperidine in chloroform with chlorine at a temperature of approximately 20 C. while it is irradiated with ultraviolet light, distilling off the chloroform and continuing the reaction of the residue With chlorine at temperatures gradually increasing to 200 C., and subsequently recovering the tetrachloropyridine and pentachloropyridine thus produced.

No references cited.

HENRY R. JILES, Primary Examiner. 

1. A PROCESS FOR THE PRODUCTION OF AN ORGANIC COMPOUND CONTAINING CHLORINE AND NITROGEN COMBINED IN THE -N=CCL-RADICAL WHICH COMPRISES (A) REACTING AN AMINO COMPOUND SELECTED FROM THE GROUP CONSISTING OF (I) AMINES OF THE FORMULA 